Induction of TGF-β1 synthesis in D-glucose primed human proximal tubular cells by IL-1β and TNFα. The aim of the present study was to examine whether the induction of TGF-β1 synthesis by the pro-inflammatory macrophage derived cytokines, IL-1β or TNFα, was modified by alterations in D-glucose concentrations. Stimulation of growth arrested HPTC with IL-1β or TNFα resulted in increased expression of TGF-β1 mRNA. The transcript was demonstrable 60 minutes after the addition of IL-1β, and apparent steady-state mRNA levels were achieved after six hours. Following stimulation with TNFα, TGF-β1 mRNA was detectable after 15 minutes and reached steady state levels by two hours. Quantitative RT-PCR revealed that following six hours stimulation with either IL-1β or TNFα (both at 1 ng/ml), there was no difference in the absolute amount of TGF-β1 mRNA induced by these two stimuli (14.8 ± 5.6 vs. 19.7 ± 4.9 pm). Despite induction of TGF-β1 mRNA following stimulation with IL-1β or TNFα, neither stimulus increased TGF-β1 protein synthesis or release. Pre-exposure of HPTC to 25 mm D-glucose for 48 hours and subsequent stimulation with IL-1β resulted in the secretion of latent TGF-β1 in both a time and dose dependent manner. This effect was not apparent following TNFα stimulation of D-glucose primed HPTC. Stimulation of TGF-β1 synthesis by IL-1β in D-glucose primed cells was inhibited by cycloheximide but not by actinomycin-D. Examination of D-glucose induced TGF-β1 mRNA revealed that IL-1β, but not TNFα, increased the stability of the D-glucose induced transcript. These results demonstrate that the interaction of D-glucose and IL-1β lead to secretion of TGF-β1 by HPTC. In contrast, such an interaction was not demonstrable between D-glucose and TNFα. This may be explained by the ability of IL-1β to stabilize D-glucose-induced TGF-β1 mRNA.